TY - JOUR
T1 - Combined effects of radiotherapy and angiostatin gene therapy in glioma tumor model
AU - Griscelli, Frank
AU - Li, Hong
AU - Cheong, Chiat
AU - Opolon, Paule
AU - Bennaceur-Griscelli, Annelise
AU - Vassal, Gilles
AU - Soria, Jeannette
AU - Soria, Claudine
AU - Lu, He
AU - Perricaudet, Michel
AU - Yeh, Patrice
PY - 2000/6/6
Y1 - 2000/6/6
N2 - The objective of the present study was to evaluate the antitumor effect of a defective adenovirus expressing a secretable angiostatin-like molecule (AdK3) in combination with radiotherapy in rat C6 gliomas s.c. preestablished into athymic mice. In vitro, the combination regimen was significantly (P < 0.001) more cytotoxic for human microcapillary endothelial cells than either treatment alone, whereas survival of C6 glioma cells was not affected in the conditions used. Radiotherapy and AdK3 gene delivery was then studied on well established C6 xenografts (165 ± 70 mm3). In these tumors, AdK3 intratumoral injections had only a marginal effect. Interestingly, when experimental radiotherapy was added, significantly higher (P < 0.005), and possibly synergistic, antitumoral effects were observed that tightly correlated a marked decrease of intratumoral vascularization. The combination of radiotherapy and AdK3 intratumoral injections also revealed a significant (P < 0.05) inhibition of tumor growth as compared with either treatment alone for larger tumors (467 ± 120 mm3). Altogether, these data emphasize the potential of combining a destructive strategy directed against the tumor cells with an anti-angiogenic approach to fight cancer.
AB - The objective of the present study was to evaluate the antitumor effect of a defective adenovirus expressing a secretable angiostatin-like molecule (AdK3) in combination with radiotherapy in rat C6 gliomas s.c. preestablished into athymic mice. In vitro, the combination regimen was significantly (P < 0.001) more cytotoxic for human microcapillary endothelial cells than either treatment alone, whereas survival of C6 glioma cells was not affected in the conditions used. Radiotherapy and AdK3 gene delivery was then studied on well established C6 xenografts (165 ± 70 mm3). In these tumors, AdK3 intratumoral injections had only a marginal effect. Interestingly, when experimental radiotherapy was added, significantly higher (P < 0.005), and possibly synergistic, antitumoral effects were observed that tightly correlated a marked decrease of intratumoral vascularization. The combination of radiotherapy and AdK3 intratumoral injections also revealed a significant (P < 0.05) inhibition of tumor growth as compared with either treatment alone for larger tumors (467 ± 120 mm3). Altogether, these data emphasize the potential of combining a destructive strategy directed against the tumor cells with an anti-angiogenic approach to fight cancer.
KW - Angiogenesis
KW - Cancer
KW - Recombinant adenovirus
UR - http://www.scopus.com/inward/record.url?scp=12944331952&partnerID=8YFLogxK
U2 - 10.1073/pnas.110134297
DO - 10.1073/pnas.110134297
M3 - Article
C2 - 10823901
AN - SCOPUS:12944331952
SN - 0027-8424
VL - 97
SP - 6698
EP - 6703
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -